title: Tumor microenvironment regulates metastasis and metastasis genes of mouse MMTV-PymT mammary cancer cells in vivo.
abstract: Metastasis is the primary cause of death in breast cancer patients, yet there are challenges to modeling this process in vivo. The goal of this study was to analyze the effects of injection site on tumor growth and metastasis and gene expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat pad, tail vein, intracardiac, and intratibial), and tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Met-1 tumors were analyzed based on morphology and changes in gene expression in each tissue microenvironment. There were 6 permissible sites of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary, bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors (highest Ki-67 index). Morphologic differences were evident in each tumor microenvironment. Finally, 7 genes were differentially expressed in the Met-1 tumors in the 6 sites of growth or metastasis. This investigation demonstrates that breast cancer progression and metastasis are regulated by not only the tumor cells but also the experimental model and unique molecular signals from the tumor microenvironment.
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Werbeck
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
authors.forename: N K
authors.initials: NK
authors.lastname: Thudi
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Martin
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
authors.forename: C
authors.initials: C
authors.lastname: Premanandan
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Cellular Biochemistry, The Ohio State University, Columbus, OH, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Ostrowksi
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA rosol.1@osu.edu.
authors.forename: T J
authors.initials: TJ
authors.lastname: Rosol
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000662:veterinary; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D052138:Genes, Neoplasm / Q000235:genetics / Q000502:physiology*; D006652:Histological Techniques / Q000662:veterinary; D007150:Immunohistochemistry / Q000662:veterinary; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D059016:Tumor Microenvironment / Q000502:physiology*
keywords: PyMT; bone; breast cancer; lung; mammary cancer; mammary tumor; metastasis; ovary